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  • Title: Long Noncoding RNA-ATB Impairs the Function of Tumor Suppressor miR-126-Mediated Signals in Endometrial Cancer for Tumor Growth and Metastasis.
    Author: Zheng X, Liu M, Song Y, Feng C.
    Journal: Cancer Biother Radiopharm; 2019 Feb; 34(1):47-55. PubMed ID: 30601064.
    Abstract:
    OBJECTIVE: Long non-coding RNA-ATB (Lnc-ATB) have been reported to promote tumor proliferation and metastasis via regulation of tumor suppressive miRNA-related signals. Patients with endometrial cancer (EC) have advanced stage disease or metastasis have poor prognosis. We here investigated the role of Lnc-ATB in endometrial cancer. METHODS: Endometrial cancer tissues and normal tissues (n = 35) were collected to determine the expression and clinical significance of Lnc-ATB, and bioinformatics analysis was used to predict the miRNA target. siRNA was used to estimate the function of Lnc-ATB in EC cell lines and in vivo. RESULT: The expression of Lnc-ATB is up-regulated in tumor tissues and EC cell lines. Patients with high expressed Lnc-ATB have high FIGO stage and poor tumor differentiation. The tumor suppressor miR-126 interacted with Lnc-ATB. Down-regulated miR-126 negative correlated with FIGO stage and tumor differentiation. Knockdown of Lnc-ATB in RL95 and HEC1A cell lines increased the miR-126 level and impaired the cell vitality, induced caspase-3-related tumor apoptosis and G1/S arrest. However, abrogation of miR-126 by its inhibitors counteracted Lnc-ATB knockdown-induced tumor inhibition via regulation of miR-126 target gene PIK3R2 and Sox2-related apoptosis and cell cycle pathway. Meanwhile, Lnc-ATB knockdown also suppressed the migration and invasion and inhibited TGF-β-induced epithelial-mesenchymal transition (EMT) phenotype via miR-126. Knockdown of Lnc-ATB in vivo remarkably induced tumor regression via restoration of tumor suppressor miR-126, leading to deceased tumor volume, reduced expression of PCNA and PIK3R2/Sox2 signals and EMT phenotype in tumor tissues. CONCLUSION: These data demonstrate the tumorigenic role of Lnc-ATBs in endometrial cancer via abrogation of tumor suppressor miR-126 signals.
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